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OBJECTIVE--Abnormal cellular cholesterol handling in islets may contribute to β-cell dysfunction in type 2 diabetes. β-Cell deficiency for the ATP binding cassette transporter Al (ABCA1), which mediates the efflux of [...]

Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability. The systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects. Measurements were performed in random order on five occasions: two control measurements, two measurements during normoinsulinemic hyperglycemia with or without N-acetylcysteine (NAC) infusion, and one during mannitol infusion. Glycocalyx measurements were reproducible (1.7 ± 0.2 vs. 1.7 ± 0.3 1). Hyperglycemia reduced glycocalyx volume (to 0.8 ± 0.2 1; P < 0.05), and NAC was able to prevent the reduction (1.4 ± 0.2 1). Mannitol infusion had no effect on glycocalyx volume (1.6 ± 0.11). Hyperglycemia resulted in endothelial dysfunction, increased plasma hyaluronan levels (from 70 ± 6 to 112 ± 16 ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 + 2: from 0.4 ± 0.1 to 1.1 ± 0.2 nmol/l; D-dimer: from 0.27 ± 0.1 to 0.55 ± 0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia., Patients with diabetes have increased vascular vulnerability to atherogenic insults, leading to accelerated atherogenesis. Although atherogenesis is in part due to the increased prevalence of traditional cardiovascular risk factors, these [...]